adenine nucleotide translocator transports haem precursors into mitochondria腺嘌呤核苷转运蛋白运输血红素前体进入线粒体.pdfVIP

Adenine Nucleotide Translocator Transports Haem Precursors into Mitochondria 1. 2. 1 3 1 Motoki Azuma , Yasuaki Kabe , Chikanori Kuramori , Masao Kondo , Yuki Yamaguchi , Hiroshi Handa1,4* 1 Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama, Japan, 2 Department of Integrative Medical Biology, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan, 3 Department of Early Childhood Care and Education, Toyoko Gakuen Women’s College, , Setagaya-ku, Tokyo, Japan, 4 Solutions Research Organization, Integrated Research Institute, Tokyo Institute of Technology, Midori-ku, Yokohama, Japan Abstract Haem is a prosthetic group for haem proteins, which play an essential role in oxygen transport, respiration, signal transduction, and detoxification. In haem biosynthesis, the haem precursor protoporphyrin IX (PP IX) must be accumulated into the mitochondrial matrix across the inner membrane, but its mechanism is largely unclear. Here we show that adenine nucleotide translocator (ANT), the inner membrane transporter, contributes to haem biosynthesis by facilitating mitochondrial accumulation of its precursors. We identified that haem and PP IX specifically bind to ANT. Mitochondrial uptake of PP IX was inhibited by ADP, a known substrate of ANT. Conversely, ADP uptake into mitochondria was competitively inhibited by haem and its precursors, suggesting that haem-related porphyrins are accumulated into mitochondria via ANT. Furthermore, disruption of the ANT genes in yeast resulted in a reduction of